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Immune checkpoint inhibitor (ICI) immunotherapy leverages the body's own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune-related adverse events (IrAEs) may lead to treatment interruption, permanent organ dysfunction, hospitalization, and premature death. Thyroiditis is one of the most common IrAEs, but the cause of thyroid IrAEs remains unknown. In this study, we use a new, physiologically relevant mouse model of ICI-associated autoimmunity to identify a key role for type 3 immune cells in the development of thyroid IrAEs. Multiple lineages of IL-17A-producing T cells expand in thyroid tissue with ICI treatment. Intrathyroidal IL-17A-producing innate-like γδT17 cells were increased in tumor-free mice, whereas adaptive Th17 cells were also prominent in tumor-bearing mice, following ICI treatment. Furthermore, Ab-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice with and without tumor challenge. Finally, combination of IL-17A neutralization with ICI treatment in multiple tumor models did not reduce ICI antitumor efficacy. These studies suggest that targeting Th17 and γδT17 cell function via the IL-17A axis may reduce IrAEs without impairing ICI antitumor efficacy and may be a generalizable strategy to address type 3 immune-mediated IrAEs.

Background: Facial feminization surgery (FFS) is critical to gender-affirming surgery, consisting of craniomaxillofacial procedures to align facial features with a patient's gender identity. Central to FFS is genioplasty, which reshapes or repositions the chin; however, limited research exists on genioplasty in FFS. This review and cohort analysis aim to evaluate current practices and outcomes for individuals undergoing FFS with genioplasty. Methods: A systematic review included transfeminine individuals undergoing FFS with genioplasty. A retrospective study reviewed FFS cases with genioplasty between 2017 and 2024. Data collected included demographics, imaging, virtual surgical planning (VSP), complications, and patient-reported outcomes (PROs). Results: The review included 12 studies with 1417 patients, with 34.2% undergoing genioplasty. The mean age was 37.3 years, and 60.1% were White. Preoperative imaging and VSP were used in 66.7% of studies, 3D-printed cutting guides in 37.5%, and 3D reconstruction in 75.0%. Reduction genioplasty was the most common technique. All PROs indicated high satisfaction, with a 2.67% revision rate. Complications were low (0.55%), with infections being most frequent (0.48%). In the institutional cohort, 351 patients underwent FFS, with 64.4% undergoing genioplasty, significantly higher than in the review (p < 0.001). Sliding genioplasty was preferred without preoperative imaging or VSP. Postoperative dissatisfaction was 3.54%, with 0.88% requiring revision (p = 0.063). Complication rates (1.77%) were similar to those of the review (p = 0.065). Conclusions: Genioplasty is important in FFS, with low complication and revision rates and high patient satisfaction. However, gaps remain in validated PROs and technique-specific outcomes. While preoperative imaging and VSP show benefits, comparable outcomes are achievable without them. [ABSTRACT FROM AUTHOR]

Importance: Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. Objective: To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. Design, Setting, and Participant: A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. Main Outcomes and Measures: Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. Results: The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. Conclusions and Relevance: This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss. This article describes the development of a microsurgical strategy for combined whole eye and facial transplant and the clinical findings during the first year following transplant. Key Points: Question: Can a combined whole eye and face transplant be safely performed maintaining viability of the allograft and retinal function? Findings: The microsurgical protocol for combined whole eye and face transplant is detailed, including ophthalmic vessel revascularization and transplant. Following transplant, evidence of globe and retinal perfusion, retinal responses to light, and lack of acute rejection were demonstrated. There was no light perception at 1 year post transplant. Meaning: The successful revascularization of the transplanted eye achieved in this study may serve as a step towards the goal of globe transplant for restoration of vision. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine a generalized outcome and risk profile for patients undergoing orthognathic surgery for the definitive treatment of cleft lip and palate. Furthermore, we hope to determine the key risk factors that cause increased risk for cleft lip and palate patients undergoing orthognathic surgery. Methods: This study includes a systematic review using PubMed, MEDLINE, Cochrane, and Scopus. Data curation utilized Covidence software, with dual-reviewer screening and conflict resolution by a third party, focusing on publications with the full texts available. Results: The initial search yielded 1697 articles. Following title, abstract, and full-text screening, a total of 62 articles were included in this review. A total of 70.9% of included articles had moderate bias, with the rest having low risk of bias. The sample consisted of 2550 patients with an average age of about 20 years and an average follow-up of 16.8 months. The most employed procedure was Le Fort I osteotomy (99%). In terms of velopharyngeal function, there were notable increases in insufficiency and severity scores, with an average 63% worsening score from the baseline. That being said, patients experienced an average 33% improvement in speech articulation. Furthermore, the average horizontal movement was reported to be 6.09 mm with a subsequent relapse of 0.98 mm overall. Conclusions: This systematic review distills data from 62 articles and 2550 patients. It highlights the efficacy of orthognathic surgery in addressing oropharyngeal and aesthetic deficits. This study identifies relapse and velopharyngeal insufficiency as recurrent complications. These insights inform surgical refinement and patient counseling, laying a foundation for enhanced clinical protocols. [ABSTRACT FROM AUTHOR]

Purpose: Facial transplantation involves partial or total replacement of neuromuscular and skeletal structures of the face, head, and neck using donor tissues and is among the most extensive facial reconstructive procedures. This case report compares changes in speech production and articulator movement in a 44-year-old man from pretransplant to a 13-month posttransplant period. Method: Speech production and articulator movement data were examined at 5 time points, once pretransplant and 4 times posttransplant (4, 7, 10, and 13 months), and compared to 4 healthy controls. A motion capture system was used to track jaw and vertical/horizontal lip movement during nonspeech and speech tasks. Speech intelligibility, jaw displacement, lip aperture, and movement variability were measured. Results: Speech intelligibility varied across the study period and was restored to control status by 7 months posttransplant. Jaw displacement and lip aperture in the vertical plane significantly increased over time for nonspeech and speech tasks. Changes in horizontal lip movements over time were minimal. Jaw and lip movement variability fluctuated over time and was greater than the controls by 13 months posttransplant. Discussion: Findings quantify changes in articulator movement and contributions to improved speech production following facial transplant. Changes reflect the adaptability of the speech motor system and are discussed in relation to pretransplant speech motor control patterns.

Face transplantation (FT) has emerged as a critical intervention for patients with complex facial deformities unsuitable for conventional reconstructive methods. It aims to restore essential functions such as facial expression, mastication, and speech, while also improving psychosocial health. The procedure utilizes various surgical principles, addressing unique challenges of craniofacial complexity and diverse injury patterns. The integration of Computerized Surgical Planning (CSP) leverages computer-aided technologies to enhance preoperative strategy, intraoperative navigation, and postoperative assessment. CSP utilizes three-dimensional computed tomography, printing, angiography, and navigation systems, enabling surgeons to anticipate challenges and reduce intraoperative trial and error. Through four clinical cases, including a groundbreaking combined face and bilateral hand transplant, CSP's role in FT is highlighted by its ability to streamline operative processes and minimize surgical revisions. The adoption of CSP has led to fewer cadaveric rehearsals, heightened operative precision, and greater alignment with preoperative plans. Despite CSP's advancements, it remains complementary to, rather than a replacement for, clinical expertise. The demand for technological resources and multidisciplinary teamwork is high, but the improved surgical outcomes and patient quality of life affirm CSP's value in FT. The technology has become a staple in reconstructive surgery, signaling a step forward in the evolution of complex surgical interventions. [ABSTRACT FROM AUTHOR]